ANaPSyS - Artifical Natural Products System Synthesis

Institutionen
  • FB Chemie
Publikationen
  Gerlinger, Christa K. G.; Gaich, Tanja (2019): Structure-Pattern-Based Total Synthesis Chemistry - A European Journal. Wiley. 2019, 25(46), pp. 10782-10791. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201901308

Structure-Pattern-Based Total Synthesis

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In this article the concept of structure-pattern-recognition and its application to total synthesis is summarized. By applying this synthetic strategy to the two biogenetically unrelated natural product families Sarpagine and Stemona alkaloids, a drastic increase of synthetic efficiency could be achieved. To highlight its potential, this strategy is compared with some elegant target-oriented syntheses. The importance of strategic planning and synthesis design is clearly demonstrated.

Forschungszusammenhang (Projekte)

  Gaich, Tanja; Rebmann, Heiko; Gerlinger, Christa K. G. (2019): Gram‐scale Total Syntheses of Sarpagine Alkaloids and non‐Natural Derivatives Chemistry - A European Journal. 2019, 25(11), pp. 2704-2707. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201805644

Gram‐scale Total Syntheses of Sarpagine Alkaloids and non‐Natural Derivatives

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This work describes the total synthesis of 3 members of the sarpagine alkaloid family and 10 non‐natural congeners via an improved synthetic sequence which was designed to the point of gram‐scale production of materials suited for SAR‐studies. Furthermore, the manuscript details how the synthetic route was used to access the biogenetically completely unrelated stemona alkaloid parvineostemonine (34), posing a showcase for efficient synthetic design.

Forschungszusammenhang (Projekte)

  Gerlinger, Christa K. G.; Krüger, Sebastian; Gaich, Tanja (2018): Total Synthesis of Parvineostemonine by Structure Pattern Recognition : A Unified Approach to Stemona and Sarpagine Alkaloids Chemistry - A European Journal. 2018, 24(16), pp. 3994-3997. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201800365

Total Synthesis of Parvineostemonine by Structure Pattern Recognition : A Unified Approach to Stemona and Sarpagine Alkaloids

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Through structure pattern recognition based total synthesis we designed a synthesis in which two biogenetically unrelated natural product families (Stemona- and Sarpagine alkaloids) share 50 % of their synthetic sequence. In this report, the efficiency of such a strategic approach is demonstrated in the total synthesis of the Stemona alkaloid parvineostemonine, proceeding through a privileged intermediate that we have previously transformed into biogenetically completely unrelated Sarpagine alkaloids. In addition, we capitalized on the symmetry properties of the privileged intermediate, which was obtained as two regioisomers. After their separation by column chromatography the two regioisomers were converted to the corresponding pair of enantiomers by one transformation. To the best of our knowledge, this feature (conversion of regioisomers to enantiomers) has never been applied to natural product synthesis, and proved to be very valuable, since it allowed to obtain both optical antipodes of parvineostemonine in a single synthetic campaign. This not only enabled the determination of the previously undisclosed absolute configuration of the natural product, but gave 60-200 mg amounts of both enantiomers of the natural product.

Forschungszusammenhang (Projekte)

  Serpeloni, Fernanda; Radtke, Karl M.; Hecker, Tobias; Elbert, Thomas (2016): Epigenetic Biomarkers of Prenatal Maternal Stress SPENGLER, Dietmar, ed., Elisabeth BINDER, ed.. Epigenetics and Neuroendocrinology : Clinical Focus on Psychiatry, Volume 2. Cham: Springer, 2016, pp. 177-196. Epigenetics and Human Health. ISBN 978-3-319-29900-6. Available under: doi: 10.1007/978-3-319-29901-3_8

Epigenetic Biomarkers of Prenatal Maternal Stress

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Diverse maternal experiences or mood disturbances before birth pose a substantial risk for poor lifetime mental health outcomes. DNA methylation variation in response to prenatal stress has been shown in animal model studies. Although prenatal time represents a sensitive period of development, little is known about the impact of maternal stress during pregnancy on DNA methylation during the life span in humans. In this review, we provide a brief summary of key human studies that bring evidence of DNA methylation in association with prenatal stress. We discuss common findings in the studies such as the type of maternal stress associated to offspring’s DNA methylation and plasticity/stability of epigenetic variations. We also suggest the contribution of additional candidate gene approaches and genome-wide DNA methylation profile, in order to further explore and define the relationship between early social environment, epigenetics, and long-term outcomes. The implications of maternal care on DNA methylation as well as the importance of maternal well-being during pregnancy to prevent future health problems are considered.

Forschungszusammenhang (Projekte)

  Krüger, Sebastian; Gaich, Tanja (2016): Total Syntheses of Vellosimine,N-Methylvellosimine, and 10-Methoxyvellosimine and Formal Synthesis of 16-Epinormacusine B through a [5+2] Cycloaddition European Journal of Organic Chemistry : EurJOC. 2016, 2016(28), pp. 4893-4899. ISSN 0075-4617. eISSN 0365-5490. Available under: doi: 10.1002/ejoc.201600870

Total Syntheses of Vellosimine,N-Methylvellosimine, and 10-Methoxyvellosimine and Formal Synthesis of 16-Epinormacusine B through a [5+2] Cycloaddition

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To date, more than 100 members of the sarpagine alkaloid family have been isolated. Their structural variations originate from oxidative transformations of the carboskeleton and the presence of both absolute configurations at the C-16 atom, which is established in the course of their biosynthesis. More than 40 sarpagine alkaloids belong to the either the 16-regular or 16-epi subgroups, depending on the stereochemistry at C-16. Herein, we report the formal synthesis of 16-epinormacusine B, a member of the 16-epi group, by using our well-established generalized strategy for the total synthesis of these alkaloids. Furthermore, we provide the synthetic details and pitfalls of the asymmetric total syntheses of vellosimine, N-methylvellosimine, and 10-methoxyvellosimine, all members of the 16-regular group.

Forschungszusammenhang (Projekte)

  Kolassa, Iris-Tatjana; Illek, Sonja; Wilker, Sarah; Karabatsiakis, Alexander; Elbert, Thomas (2015): Neurobiological Findings in Post-traumatic Stress Disorder SCHNYDER, Ulrich, ed. and others. Evidence based treatments for trauma-related psychological disorders : a practical guide for clinicians. Cham [u.a.]: Springer, 2015, pp. 63-86. ISBN 978-3-319-07108-4. Available under: doi: 10.1007/978-3-319-07109-1_4

Neurobiological Findings in Post-traumatic Stress Disorder

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Post-traumatic stress disorder (PTSD) symptoms are present across cultures, with the only differences being the indigenous ways in which affected individuals deal with them. Hence, there must be a common underlying basis for these symptoms. The development of an intense memory for the traumatic experiences encountered, and associated neurobiological alterations, may explain the cross-cultural occurrence of similar PTSD symptoms.

This chapter presents selected neurobiological findings in post-traumatic stress disorder (PTSD) in the framework of a neurobiological model of PTSD, the fear network model, which explains the development of strong associative emotional-sensory memories for traumatic events. With repeated exposure to traumatic stressors, this associative network gets strengthened but at the same time detached from the corresponding contextual information. After introducing this theoretical background, we next review current knowledge on genetic risk factors for PTSD development, followed by epigenetic alterations found in trauma survivors with PTSD. This is followed by a section on physiological alterations associated with a diagnosis of PTSD. We elaborate on structural and functional alterations in the brain of trauma survivors with PTSD, which correspond well with the assumptions of the fear network model. Furthermore, we summarize evidence that trauma exposure and subsequent PTSD can have adverse physical health consequences, such as cardiovascular, cerebrovascular, gastrointestinal, musculoskeletal, inflammatory, and autoimmune diseases, and accelerate the aging process, increasing the risk for the earlier onset of age-related diseases. We illustrate on a molecular level which processes increase disease risk in traumatized populations. Finally, we show that at least some PTSD-associated molecular alterations might be reversible through treatment.

Forschungszusammenhang (Projekte)

Mittelgeber
Name Finanzierungstyp Kategorie Kennziffer
Europäische Union Drittmittel Forschungsförderprogramm 510/16
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Laufzeit: 01.04.2016 – 31.03.2021